This work involves the regulation of brain and cerebrospinal (CSF) acid-base and electrolyte balance in newborns and adults, the mechanisms involved and how this regulation relates to the control of breathing. The work is progressing in three basic ways. 1) Descriptive studies in human premature and term newborns and in puppies of CSF acid-base regulation and mechanistic studies in whole animals, newborn and adult, of the role of the blood-brain-barrier and of brain cells in this regulation. 2) Studies of transformed nerve and glial cell lines grown in culture to ascertain their general and relative roles in brain acid-base and electrolyte regulation. 3) Studies of the control of breathing in the potassium (K) depleted rat, a prototype of a situation with alterations in brain acid-base and electrolyte balance and in the control of breathing. This animal model besides its still unexplained abnormalities in respiratory control has led to the study of the role of central and peripheral adrenergic mechanisms in the control of breathing.